1.A small molecule, Lys-Ala-7-amido-4-methylcoumarin, facilitates RNA dimer maturation of a stem-loop 1 transcript in vitro: structure-activity relationship of the activator.
Chung J1, Mujeeb A, Jiang Y, Guilbert C, Pendke M, Wu Y, James TL. Biochemistry. 2008 Aug 5;47(31):8148-56. doi: 10.1021/bi800230m. Epub 2008 Jul 11.
The type 1 human immunodeficiency virus (HIV-1), like all retroviruses, contains two copies of the RNA genome as a dimer. A dimer initially forms via a self-complementary sequence in the dimer initiation site (DIS) of the genomic RNA, but that dimer is converted to a mature dimer in a process generally promoted by the viral nucleocapsid (NC) protein. Formation of the mature dimer is correlated with infectivity. Study of genomic dimerization has been facilitated by discovery of short RNA transcripts containing the DIS stem-loop 1 (SL1), which can dimerize spontaneously without any protein factors in vitro as well as via the NC protein. On the basis of the palindromic nature of the apical loop of SL1, a kissing loop model has been proposed. First, a metastable kissing dimer is formed via a loop-loop interaction and then converted into a more stable extended dimer by the NC protein. This dimerization process in vitro is believed to mimic the in vivo RNA maturation.
